General anesthesia is a medically induced coma and loss of protective reflexes resulting from the administration of one or more anesthetic agents. General anesthesia enables a patient to tolerate surgical procedures that would otherwise inflict unbearable pain or enables surgeons to perform complex procedures by ensuring that the patient does not move during surgery.
Adequate dosage of anesthetic agents during general anesthesia is essential. Underdosage of anesthetics may lead to an insufficient depth of anesthesia and thereby increases the risk of intraoperative awareness. Overdosage, on the other hand, may result in overly deep anesthesia and can even have toxic effects on the patient. Thus, precise monitoring of the blood level of anesthetics is indispensable.
Anesthetic agents may be administered by various routes, e.g. by injection, inhalation, oral administration or rectal administration.
Anesthetics applied by inhalation (inhalational anesthetics) typically show very steep dose-response curves and have the advantage that the depth of anesthesia can be rapidly altered by changing the inhaled concentration of the anesthetic. This means, however, that tight monitoring of the blood level of such inhalational anesthetics is of particular importance.
In inhalation anesthesia during surgical procedures carried out in the absence of a heart-lung machine (cardiopulmonary bypass machine), the blood level of inhalational anesthetics can be monitored by analysis of inspiratory and end-expiratory respiratory gases. The end-expiratory concentration of an inhalational anesthetic agent equals the alveolar concentration which, provided unrestricted pulmonary perfusion, correlates with the blood concentration of the inhalational anesthetic. In clinical practice, the end-expiratory concentration of inhalational anesthetics is therefore often used as surrogate parameter for the blood concentration of the inhalational anesthetic. A prerequisite for successful implementation of this approach is, however, unrestricted blood flow through the lungs of the patient.
Due to, amongst other reasons, the cardioprotective properties of certain inhalational anesthetics, anesthesia with inhalational anesthetic agents has also become a valued option for surgical interventions carried out in the presence of a heart-lung machine. A heart-lung machine is used to establish an extracorporeal circulation (ECC) system in surgical procedures that may necessitate the interruption or cessation of blood flow in the body, a critical organ (such as the heart, lungs or liver) or great blood vessel (such as the aorta, pulmonary artery, pulmonary veins or vena cava), e.g. in coronary artery bypass grafting (CABG) surgery, in particular in cardiac bypass surgery. The heart-lung machine temporarily assumes the functions of the heart and lungs of the patient, wherein the function of the heart, i.e. pumping the blood, is taken over by a mechanical pump, and the function of the lungs, i.e. supplying the blood with oxygen and eliminating accumulating carbon dioxide, is taken over by an oxygenator (N. Kouchoukos et al., Kirklin and Baratt-Boyes: Cardiac Surgery, 4th ed., Saunders (2013); J. Kaplan et al., Kaplan's Cardiac Anesthesia, 6th ed., Saunders (2011)). (Besides surgical interventions in the presence of a heart-lung machine, extracorporeal circulation in the presence of an oxygenator is also used in other medical procedures, for example during extracorporeal membrane oxygenation (ECMO) or pumpless extracorporeal lung assist (PECLA).)
An oxygenator comprises an oxygenating chamber in which gas exchange between a gas flow providing a supply of fresh gas and the blood of a patient takes place. Blood from the body of the patient is pumped to the oxygenator, enters the oxygenating chamber through a blood inlet, passes through the oxygenating chamber, leaves the oxygenating chamber again through a blood outlet and is returned from the oxygenator to the patient. Moreover, a gas flow of fresh gas enters the oxygenating chamber through a gas inlet, is passed through the oxygenating chamber and leaves the oxygenating chamber again through a gas outlet. In the oxygenating chamber, oxygen (and, if present in the gas flow, other gases such as inhalational anesthetics) are transferred from the gas flow into the blood, while other gases, such as carbon dioxide, are transferred from the blood into the gas flow.
There are several types of oxygenators that differ by the way how gas exchange in the oxygenating chamber is accomplished. In bubble oxygenators, gas exchange in the oxygenating chamber is achieved by bubbling the gas of the gas flow through the blood, thus allowing for direct diffusion between the gas bubbles and the blood. Modern-day oxygenators are, however, usually membrane oxygenators in which gas exchange in the oxygenating chamber occurs through a semi-permeable membrane that is permeable to gases like oxygen, carbon dioxide or inhalational anesthetics, but impermeable to blood. Typically, the oxygenating chamber of such a membrane oxygenator comprises a system of hollow fibers formed from the semi-permeable membrane (or, alternatively, membranes formed in other hollow shapes, such as hollow sheets). A gas flow is passed through the inside lumen of the hollow fibers, while blood flows by on the outside of the hollow fibers. Oxygen (and, if present in the gas flow, other gases) diffuse from the gas flowing inside the hollow fibers down their concentration gradient across the membrane wall of the fibers into the blood flowing outside the hollow fibers, while gases that are present in the blood in high concentration, such as carbon dioxide, diffuse down their concentration gradient from the blood into the gas flowing inside the fibers and are removed when the gas flow leaves the oxygenation chamber.
In order to administer an inhalational anesthetic agent to a patient undergoing extracorporeal circulation involving an oxygenator, the inhalational anesthetic can be admixed to the gas flow before leading it through the oxygenating chamber, thus resulting in transfer of the inhalational anesthetic from the gas flow into the blood of the patient. If the inhalational anesthetic agent is a volatile anesthetic, the volatile anesthetic may be vaporized with a vaporizer prior to admixing it to the gas flow.
For inhalation anesthesia of a patient under extracorporeal circulation, the inhalational anesthetic is admixed to the flow of fresh gas fed into the oxygenator of the heart-lung machine at a selected concentration (such as 2% by volume of sevoflurane) and enters the blood of the patient through the oxygenator membrane which is permeable to the inhalational anesthetic. Since under extracorporeal circulation the lungs are not or not fully perfused, it is not possible during ECC to monitor the depth of an anesthesia with inhalational anesthetics by analysis of end-expiratory respiratory gases from the lungs. Alternative methods for monitoring the depth of anesthesia, such as repeated measurement of the concentration of inhalational anesthetics in whole blood by gas chromatography, are not practically feasible.
An alternative approach that has been pursued is to measure the concentration of inhalational anesthetics in the exhaust gas flow of the oxygenator. However, this method can at best be used to verify if a setting at the vaporizer used for vaporizing a volatile anesthetic results in approximately the desired concentration of volatile anesthetic in the flow of fresh gas that is used for gas exchange in the oxygenator. It does not allow accurate conclusions about the amount of inhalational anesthetic that is present in the blood of the patient.